Does Caloric Restriction Alone Explain the Effects of Roux-en-Y Gastric Bypass on Glucose Metabolism? Not by a Long Limb

  1. Adrian Vella
  1. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota
  1. Corresponding author: Adrian Vella, vella.adrian{at}

Among patients with type 2 diabetes, bariatric surgery has been the subject of considerable interest because of its favorable effects on glucose metabolism. Indeed, various procedures have been associated with high rates of diabetes remission (1), although the outcomes of these studies have been assessed in a heterogeneous manner (2). Despite the favorable results overall, there has been divergence among procedures regarding improvement of diabetes (1). This observation raises the possibility of identifying underlying mechanisms leading to improved glucose metabolism as a means to identify new diabetes treatments. The pathophysiology underlying development of type 2 diabetes includes defects in insulin secretion, disordered postprandial suppression of glucagon secretion, and defects in insulin action and glucose effectiveness (the ability of insulin and glucose to stimulate glucose uptake and suppress glucose release) (3). The heterogeneous effects of various forms of bariatric surgery on these parameters remain a topic of intense interest.

Roux-en-Y gastric bypass (RYGB) is currently the most common bariatric procedure. This surgical approach results in both gastric restriction and malabsorption. Increased delivery of calories to the jejunum/ileum increases enteroendocrine secretion, most notably that of glucagon-like peptide-1 (GLP-1) (4). Whether the increase in postprandial concentrations of GLP-1 is relevant to insulin secretion or gastrointestinal motility in ways that benefit glucose metabolism after gastric bypass is uncertain. GLP-1 increases insulin secretion and suppresses glucagon secretion. In an intact upper gastrointestinal tract, GLP-1 also delays gastric emptying (5) and increases gastric accommodation (6). However, …

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